Rhein–Gastrodin Ester-Loaded ZIF-8 Nanosystem for the Treatment of Bacteria-Infected Wounds

Skin traumatic infections are prone to cause delayed healing or systemic infection. Conventional treatments are limited by antibiotic resistance, low bioavailability of natural drugs, and other factors, making the development of innovative antibacterial and pro-healing delivery systems of great significance. In this study, Rhein–Gastrodin ester (GR-NPs) was synthesized via the EDC/DMAP method, and a ZIF-8-loaded nanocomposite system (ZIF-8@GR-NPs) was prepared by the solvothermal method. Physicochemical characterization was completed, and in vitro and in vivo activity evaluations were simultaneously carried out. The results showed that the nanosystem exhibited a regular squarish-round morphology with a particle size of approximately 150 nm, good stability, and sustained drug release properties. In vitro, it displayed excellent antibacterial and anti-inflammatory activities capable of inhibiting pathogenic bacterial proliferation and alleviating cellular inflammatory responses. In vivo, it possessed favorable biocompatibility and could significantly facilitate the healing of traumatized and infected wounds (the healing rate was 99.82% on the 10th day postsurgery, which was significantly higher than that of the control group). Histological analysis and transcriptome RNA sequencing analysis indicated that ZIF-8@GR-NPs could inhibit the release of pro-inflammatory factors, upregulate the expression of anti-inflammatory factors, promote angiogenesis, and collagen fiber remodeling, thereby creating a favorable microenvironment for wound healing. In conclusion, ZIF-8@GR-NPs integrate the triple functions of antibacterial activity, anti-inflammatory effect, and pro-angiogenesis, providing an innovative therapeutic strategy for the clinical treatment of complex bacterial-infected wounds.